Subcellular partitioning of Nhlh2 mRNA reveals how SNORD116 loss contributes to Prader-Willi Syndrome
Year: 2026
Type: preprint
Abstract: Summary Deletion of the SNORD116 non-coding RNA is associated with the development of Prader-Willi Syndrome (PWS). We and others have identified NHLH2/Nhlh2 as a putative SNORD116/Snord116 target and in this study report that Nhlh2 and Snord116 are co-expressed in forebrain neurons. Nhlh2 mRNA is found predominantly in the nucleus of Snord116+ hypothalamic neurons but is evenly distributed between the nuclear and cytoplasmic compartments in Snord116- neurons. A hypothalamic cell line co-expressing Nhlh2 and Snord116 recapitulates this nuclear partitioning pattern for Nhlh2 only when the putative Snord116 binding site is present in the 3’ untranslated region of the Nhlh2 mRNA. In a PWS mouse model (Snord116 del ), Nhlh2 mRNA levels are unchanged in Pomc neurons but are reduced and primarily cytoplasmic in lateral hypothalamic neurons. These findings demonstrate that Snord116 regulates mRNA levels via mRNA partitioning, fundamentally altering our understanding of gene expression networks in PWS. Highlights Snord116 snoRNA and its mRNA target Nhlh2 are co-expressed in forebrain neurons. Nhlh2 mRNA is predominantly nuclear co-localized in hypothalamic Snord116+ neurons. A putative Snord116 binding site is within the region required for cellular partitioning. Nhlh2 partitioning is lost in Snord116 del mice, a model of Prader-Willi Syndrome.
Institutions: Virginia Tech, Colorado State University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7125587889